Functional Connectivity Network Disruption Underlies Domain-Specific Impairments in Attention for Children Born Very Preterm.
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ABSTRACT: Attention problems are common in school-age children born very preterm (VPT; < 32 weeks gestational age), but the contribution of aberrant functional brain connectivity to these problems is not known. As part of a prospective longitudinal study, brain functional connectivity (fc) was assessed alongside behavioral measures of selective, sustained, and executive attention in 58 VPT and 65 full-term (FT) born children at corrected-age 12 years. VPT children had poorer sustained, shifting, and divided attention than FT children. Within the VPT group, poorer attention scores were associated with between-network connectivity in ventral attention, visual, and subcortical networks, whereas between-network connectivity in the frontoparietal, cingulo-opercular, dorsal attention, salience and motor networks was associated with attention functioning in FT children. Network-level differences were also evident between VPT and FT children in specific attention domains. Findings contribute to our understanding of fc networks that potentially underlie typical attention development and suggest an alternative network architecture may help support attention in VPT children.
Project description:BackgroundPreterm infants are at risk for functional impairments in motor, cognitive, and behavioral development that may persist into childhood. The aim of this study was to determine the co-occurrence of cognitive impairments in multiple cognitive domains at school age in very preterm born children compared to term-born children.MethodsComparative study including 60 very preterm-born children (gestational age ≤ 32 weeks) and 120 term-born controls. At school age, we assessed intelligence with the WISC-III, and visuomotor integration with the NEPSY-II, verbal memory with the AVLT, attention with the TEA-ch, and executive functioning with the BRIEF. We investigated co-occurrence of various abnormal (<5th percentile) and suspect-abnormal (<15th percentile, including both suspect and abnormal) cognitive functions.ResultsAt mean age 8.8 years, 15% of preterm children had abnormal outcomes in multiple cognitive functions (≥2), versus 3% of the controls (odds ratio, OR 4.65, 95%-confidence interval, CI 1.33-16.35). For multiple suspect-abnormal cognitive outcomes, rates were 55% versus 25% (OR 3.02, 95%-CI 1.49-6.12). We found no pattern of co-occurrence of cognitive impairments among preterm children that deviated from term-born controls. However, low performance IQ was more frequently accompanied by additional cognitive impairments in preterms than in controls (OR 5.43, 95%-CI 1.75-16.81).ConclusionsA majority of preterm children showed co-occurrence of impairments in multiple cognitive domains, but with no specific pattern of impairments. The occurrence of multi-domain cognitive impairments is higher in preterms but this seems to reflect a general increase, not one with a pattern specific for preterm-born children.
Project description:Individuals born very preterm (<32 weeks gestation) are at increased risk for neuromotor impairments. The ability to characterize the structural and functional mechanisms underlying these impairments remains limited using existing neuroimaging techniques. Resting state-functional magnetic resonance imaging (rs-fMRI) holds promise for defining the functional network architecture of the developing brain in relation to typical and aberrant neurodevelopment. In 58 very preterm and 65 term-born children studied from birth to age 12 years, we examined relations between functional connectivity measures from low-motion rs-fMRI data and motor skills assessed using the Movement Assessment Battery for Children, 2nd edition. Across all subscales, motor performance was better in term than very preterm children. Examination of relations between functional connectivity and motor measures using enrichment analysis revealed between-group differences within cerebellar, frontoparietal, and default mode networks, and between basal ganglia-motor, thalamus-motor, basal ganglia-auditory, and dorsal attention-default mode networks. Specifically, very preterm children exhibited weaker associations between motor scores and thalamus-motor and basal ganglia-motor network connectivity. These findings highlight key functional brain systems underlying motor development. They also demonstrate persisting developmental effects of preterm birth on functional connectivity and motor performance in childhood, providing evidence for an alternative network architecture supporting motor function in preterm children.
Project description:Very preterm birth is associated with an increased prevalence of attention problems and may especially impair executive attention, i.e., top-down control of attentional selection in situations where distracting information interferes with the processing of task-relevant stimuli. While there are initial findings linking structural brain alterations in preterm-born individuals with attention problems, the functional basis of these problems are not well understood. The present study used an fMRI adaptation of the Attentional Network Test to examine the neural correlates of executive attention in a large sample of N = 86 adults born very preterm and/or with very low birth weight (VP/VLBW), and N = 100 term-born controls. Executive attention was measured by comparing task behavior and brain activations associated with the processing of incongruent vs. congruent arrow flanker stimuli. Consistent with subtle impairments of executive attention, the VP/VLBW group showed lower accuracy and a tendency for increased response times during the processing of incongruent stimuli. Both groups showed similar activation patters, especially within expected fronto-cingulo-parietal areas, but no significant between-group differences. Our results argue for a maintained attention-relevant network organization in high-functioning preterm born adults in spite of subtle deficits in executive attention. Gestational age and neonatal treatment variables showed associations with task behavior, and brain activation in the dorsal ACC and lateral occipital areas, suggesting that the degree of prematurity (and related neonatal complications) has subtle modulatory influences on executive attention processing.
Project description:Cortical resting state networks have been consistently identified in infants using resting state-functional connectivity magnetic resonance imaging (rs-fMRI). Comparable studies in adults have demonstrated cerebellar components of well-established cerebral networks. However, there has been limited investigation of early cerebellar functional connectivity. We acquired non-sedated rs-fMRI data in the first week of life in 57 healthy, term-born infants and at term-equivalent postmenstrual age in 20 very preterm infants (mean birth gestational age 27 ± 2 weeks) without significant cerebral or cerebellar injury. Seed correlation analyses were performed using regions of interests spanning the cortical and subcortical gray matter and cerebellum. Parallel analyses were performed using rs-fMRI data acquired in 100 healthy adults. Our results demonstrate that cortico-cerebellar functional connectivity is well-established by term. Intra- and cortico-cerebellar functional connectivity were largely similar in infants and adults. However, infants showed more functional connectivity structure within the cerebellum, including stronger homotopic correlations and more robust anterior-posterior anticorrelations. Prematurity was associated with reduced correlation magnitudes, but no alterations in intra- and cortico-cerebellar functional connectivity topography. These results add to the growing evidence that the cerebellum plays an important role in shaping early brain development during infancy.
Project description:Language deficits are reported in preterm born children across development. Recent neuroimaging studies have found functional alterations in large-scale brain networks underlying these language deficits, but the early childhood development of the language network has not been investigated. Here, we compared intrinsic language network connectivity in 4-year-old children born VPT and term-born controls, using defined language regions (Broca's area, Wernicke's areas, and their homologues in the right hemisphere). Resting-state functional magnetic resonance imaging (fMRI) was obtained, and the group differences in whole-brain connectivity were examined from each seed as well as correlations with language outcomes. We found significantly decreased functional connectivity in almost all language regions in children born VPT compared to their term controls. Notably, Broca's area homologue in the right hemisphere emerged as a functional hub of decreased connectivity in VPT group, specifically to bilateral inferior frontal and supramarginal gyri; connectivity strength between Broca's area homologue with the right supramarginal and the left inferior frontal gyri was associated with better language outcomes at 4 years of age. Wernicke's area and its homologue also showed decreased inter-hemispheric connections to bilateral supramarginal gyri in the VPT group. Decreased intra- and inter-hemispheric connectivity among primary language regions suggests immature and altered function in the language network in children born VPT.
Project description:Survivors of preterm birth experience long-lasting behavioral problems characterized by increased risk of depression, anxiety, and impairments in social functioning. The amygdala is a key region for social functioning and alterations in amygdala structure and connectivity are thought to underlie social functioning deficits in many disorders, including preterm birth. However, functional connectivity of the amygdala and its association with social impairments is not well-studied in preterm participants (PTs). In a group of late adolescents born very PT (600-1250 g birth weight), measures of social and emotional development were examined using the Child Behavior Checklist (CBCL) administered at age 16 (66 term and 161 preterm participants), the Youth Self Report (YSR) administered at age 16 (56 term and 45 preterm participants), and the Vineland Adaptive Behavior Scales (VABS) administered at age 18 (71 term and 190 preterm participants). Amygdala functional connectivity was also examined using resting-state functional magnetic resonance imaging at age 20 (17 term and 19 preterm participants). By parent report, preterm-born adolescents demonstrate increased social impairment compared to their term-born peers. Amygdala connectivity is altered for those prematurely-born, and markers of social functioning correlate with altered amygdala-PCC connectivity. These findings add to knowledge regarding the developmental trajectory of amygdala connectivity in PT and suggest a possible neural underpinning for the well-characterized social impairment experienced by prematurely-born individuals.
Project description:Adolescents born very preterm have an increased risk for anxiety, social difficulties and inattentiveness, i.e. the 'preterm behavioural phenotype'. The extreme end of these traits comprises the core diagnostic features of attention and hyperactivity disorders and autism spectrum disorder, which have been reported to show aberrant dynamic resting-state functional network connectivity. This study aimed to compare this dynamism between adolescents born very preterm and controls. A resting-state functional magnetic resonance imaging was performed on 24 adolescents born very preterm (gestational age <32 weeks and/or birth weight ≤1500 g) and 32 controls born full term (≥37 weeks of gestation) at 13 years of age. Group-wise comparisons of dynamic connectivity between the resting-state networks were performed using both hard clustering and meta-state analysis of functional network connectivity. The very preterm group yielded a higher fraction of time spent in the least active connectivity state in hard clustering state functional network connectivity, even though no group differences in pairwise connectivity patterns were discovered. The meta-state analysis showed a decreased fluidity and dynamic range in the very preterm group compared with controls. Our results suggest that the 13-year-old adolescents born very preterm differ from controls in the temporal characteristics of functional connectivity. The findings may reflect the long-lasting effects of prematurity and the clinically acknowledged 'preterm behavioural phenotype'.
Project description:The formation of resting-state functional networks in infancy has been reported to be strongly impacted by very preterm birth. Studies in childhood and adolescence have largely focused on language processing networks and identified both decreased and increased functional connectivity. It is unclear, however, whether functional connectivity strength is altered globally in children and adolescents born very preterm and whether these alterations are related to the frequently occurring cognitive deficits. Here, resting-state functional MRI was assessed in a group of 32 school-aged children and adolescents born very preterm with normal intellectual and motor abilities and 39 healthy term-born peers. Functional connectivity within and between a comprehensive set of well-established resting-state networks was compared between the groups. IQ and executive function abilities were tested with standardized tasks and potential associations with connectivity strength were explored. Functional connectivity was weaker in the very preterm compared to the term-born group between the sensorimotor network and the visual and dorsal attention network, within the sensorimotor network and within the central executive network. In contrast, functional connectivity was stronger in the very preterm group between the sensorimotor network and parts of the salience and the central executive network. Little evidence was found that these alterations underlie lower IQ or poorer executive function abilities. This study provides evidence for a long-lasting impact of very preterm birth on the organization of resting-state networks. The potential consequence of these alterations for other neurodevelopmental domains than the ones investigated in the current study warrants further investigation.
Project description:Very preterm born (VPT) children are those born before 32/40?weeks' gestational age and comprise 10% of the 15 million babies born prematurely worldwide each year. Due to advancements in neonatal medicine, the survival rate of VPT birth has increased, but few studies have investigated the nonmedical, social-cognitive morbidities that affect these children. In this study, we examined emotional face processing networks in VPT compared to age and sex matched full-term born (FT) children. Magnetoencephalography (MEG) was used to test VPT and FT born children at 6?years (n = 78) and 8?years (n = 83). Children were assessed using an implicit emotion face-processing task. Happy, fearful, and angry faces were presented for 150?ms, but children were asked to respond by button press to the location of a control pixelated image of the face displayed on the side of the screen opposite to the face. Children rated the valence of the images on a five-point scale. Group differences showed that VPT children rated angry faces more positively than their FT peers. VPT children had reduced connectivity for angry and fearful faces at 8?years in networks including regions such as the bilateral amygdala, superior temporal sulci, and anterior cingulate gyrus. Interventions should target both emotion recognition, as well as higher cognitive processes related to emotional control and thinking about one's own emotions.
Project description:Very preterm birth is associated with attention deficits that interfere with academic performance. A better understanding of attention processes is necessary to support very preterm born children. This study examined voluntary and involuntary attentional control in very preterm born adolescents by measuring saccadic eye movements. Additionally, these control processes were related to symptoms of inattention, intelligence, and academic performance. Participants included 47 very preterm and 61 full-term born 13-years-old adolescents. Oculomotor control was assessed using the antisaccade and oculomotor capture paradigm. Very preterm born adolescents showed deficits in antisaccade but not in oculomotor capture performance, indicating impairments in voluntary but not involuntary attentional control. These impairments mediated the relation between very preterm birth and inattention, intelligence, and academic performance.